Plasma heparin activity

Dextran 70 seems to be as effective as subcutaneous heparin, but is easier to administer and puts less of a burden on nursing services. Measured blood loss is similar in patients given dextran, low-dose heparin or pre-operative warfarin. Few patients given dextran or low-dose heparin seem to bleed excessively. In one study, bleeding was associated with higher levels of plasma-heparin activity (30 ). 

Specihc poly anions such as dextran sulfate (DS) appear to exhibit strong anti-HIV activity in vitro [36,37]. Human oral administration of DS is poorly absorbed, but intravaneous administration does result in increased plasma lipolytic activity [38]. Poly anions that have been considered for intravaginal anti-HIV activity include DS, carrageenan, heparin, heparan sulfate, dermatan sulfate, pentosan polysulfate, fucoidan chondroitin sulfate, keratan sulfate, and PAVAS [21,22,39,40],... 

This pentasaccharide sequence induces a conformational change in AT III which probably causes the complex to be more accessible to the active site of the proteases. The most relevant protease affected by the pentasaccharide 3 is factor Xa, but factor Xlla and plasma kallikrein activities can also be potentiated. Sequence 3 occurs in heparin as well as in various heparan sulfate proteoglycans of different origin including the vascular endothelium. 

One can see (Fig. 3) that the amount of heparin eluted, if eluted at all, is so small that it cannot account for the clotting time observed. After the copolymers are exposed to plasma, their activity decreases and may be restored only by special treatment. 

F4. Freeman, L., Engelberg, H., and Dudley, A., Plasma heparin levels I. A method for determination of plasma heparin based on anticoagulant activity. Am.. Clin. Pathol. 24, 599-606 (1954). 

The rate of triglyceride output from the plasma is mainly controlled by the lipoprotein lipase activity of peripheral tissues. Post-heparin plasma lipolytic activity in vitamin-C-deficient guinea pigs decreases considerably. In addition, in some of the animals the response of the plasma lipolytic activity to intravenously administered heparin is also prolonged (45). Similar results have been reported in vitamin-C-deficient baboons (46). 

There are currently no published data regarding EL mass or activity levels in human plasma. Indeed, there has been relatively little study of phosphohpase activity in human plasma. Phospholipase activity increases after administration of heparin [24]. Some of the phospholipase activity in human plasma [25] has been attributed to lecithin-cholesterol acyltransferase (LCAT) [26] and hepatic lipase [27]. In the presence of inflammation, the secretory phospholipase A2 (sPLA2) may account for some of the plasma phosphohpase achvity and is also increased after heparin administration [28]. The contribuhon of endofhehal hpase to plasma phospholipase activity is unknown, but fhe decrease in post-heparin phosphohpase activity in EL knockout mice suggests that EL may contribute substantiaUy to plasma phosphohpase activity in humans. 

Studies have shown that heparin is able to exert several different biological activities. In addition to the one of interest for this review, an anticoagulant effect, heparin has the ability to increase plasma lipoprotein activity, both inhibit and stimulate the alternate pathway complement activation, and enhance the release of collagenase from bone in tissue culture (S17). It has also been associated with thrombocytopenia. Several recent reviews on heparin are available (C13, T7, T8). 

While heparin increases the temperature stability of trypsin and thrombin, it increases the instability of /3-amylase, even though it shows no immediate inhibition. A slow reaction occurs leading to irreversible inactivation of amylase, probably due to salt formation followed by denaturation of the protein with the formation of higher complexes . Heparin has no effect on the serum or plasma amylase activities . 

Anticoagulant activity in vitro calculated from the number of micrograms of dextran sulphate and heparin required to give 50 per cent inhibition of coagulation of 1 ml. dog plasma. Anticoagulant activity in vivo calculated from Lee and White clotting times at 0, 1, 2, 3 hours after intravenous injection in rabbits of 3 mg/kg. Peak = peak clotting times. Area = area under the curve with formula of Millar, Jaques and Henriet suitably modified. Values for heparin were activity in vitro, 3-5 g in vivo, peak = 100 (92-108) minutes area = 0-20 LDg = 220 42 mg/kg. 

Figure 6. APTT heparin activity assay curve. Key 9, control heparinized plasma (units mL plasma) calibration APTT and O, derivatized heparin (at known weight concentrations, mg/mL plasma) APTT.

After determining the control heparin-APTT response curve, derivatized heparin was added to unheparinized bovine plasma (the same plasma used for preparing the control response curve) at known weight concentrations, and APTT was determined. Based on the interpolated heparin activity (units/mL plasma) of the derivatized heparin at known weight concentration (mg/mL plasma), the anticoagulant activity (units/mg) of the N-acetylated and hydroxyl- and carboxylic-derivatized heparins was determined. 

Berr, F., Eckel, F., and Kern, F., Jr. (1985). Plasma decay of chylomicron remnants is not affected by heparin-stimulated plasma lipolytic activity in normal fasting man. J. Lipid Res. 26, 852-859. 

Brack MJ, More RS, Hulmer PJB, Gerschlick AH. The effect of low dose nitroglycerine on plasma heparin ccmcentrations and activated partial thromboplastin times. BloodCoagFibri-wo/(1993)4,183-6. 

The diagnosis of primary hyperlipoproteinaemia can usually be confirmed, after exclusion of secondary causes, by an investigation of medical history, analysis (by electrophoresis and determination of blood lipids) of lipoprotein patterns and screening of near relatives. Further ambiguities may be removed by such procedures as the measurement of post-heparin plasma lipolytic activity or assay of LDL receptor function in cultured fibroblasts or blood lymphocytes. 

Four naturally occurring thrombin inhibitors exist in normal plasma. The most important is antithrombin III (often called simply antithrombin), which contributes approximately 75% of the antithrombin activity. Antithrombin III can also inhibit the activities of factors IXa, Xa, XIa, Xlla, and Vila complexed with tissue factor. a2-Macroglobulin contributes most of the remainder of the antithrombin activity, with heparin cofactor II and aj-antitrypsin acting as minor inhibitors under physiologic conditions. 

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